Placental TLR/NLR expression signatures are altered with gestational age and inflammation

Objective: To quantify changes in placental expression of Toll-like receptors (TLRs) and nuclear oligomerization domain (NOD)-like receptors (NLRs) gene with (1) advancing gestational age (GA) and (2) exposure to chorioamnionitis (CA) and preterm premature rupture of membrane (PPROM).

Methods: Placental tissue was collected at the time of birth from 83 subjects with live birth pregnancies from 24- to 40-week gestation between 2009 and 2013. Real-time RT-PCR analysis of 13 TLR/NLR genes involved in bacterial sensing was performed using specific probes.

Results: Of 83 patients enrolled, 61 were preterm (<37 weeks). 23 (27%) had evidence of CA; and 33 (39.8%) had PPROM. 15 (18%) had both CA and PPROM (CP). 42 (50%) had neither CA nor PPROM (C/P). Only RIPK2 (p = 0.0025) and TLR4 (p = 0.0005) were found to increase progressively with GA. We found significant changes in TLR5 (p = 0.01) with CA, NFKBIA (p = 0.016) with PPROM, NKKBIA (p = 0.003), and NFKB1 (p = 0.009) with CA and PPROM.

Conclusion: RIPK2 (mediator of NOD-dependent NF-kB signaling) and TLR4 progressively increased with GA. We speculate this upregulation may be involved in initiating labor and delivery at term. Increase in NFKBIA seen in PPROM and CA might represent a counter regulatory mechanism to decrease inflammation in these conditions. This study provides new information on relationships between GA, CA/PPROM, and TLR/NLR signaling in the placenta.